Genotype-guided platelet inhibition improves STEMI outcomes

Bedside genotype testing for mutations in the CYP2C19 gene helps select a better P2Y12 inhibitor treatment strategy for patients with ST-segment elevation myocardial infarction (STEMI) and leads to better outcomes relative to conventional therapy, a recent study has found.

The researchers conducted a prospective randomized clinical trial including 687 STEMI patients who received either genotype-guided (n=375) or standard (n=312) P2Y12 inhibitor therapy. The former group underwent genotyping for loss-of-function CYP2C19 alleles; carriers were given ticagrelor while noncarriers were prescribed clopidogrel. In contrast, all standard-treatment participants received clopidogrel.

Of the 375 patients who underwent genotyping, 31.5 percent were found to harbour loss-of-function mutations and were deemed to be either intermediate or poor metabolisers of clopidogrel. However, only 9.1 percent of patients in the genotype-guided group were given ticagrelor, and clopidogrel remained the dominant treatment prescribed (90.9 percent) even after considering mutational status.

Nevertheless, genotyping continued to significantly reduce the risk of the primary composite outcome, consisting of myocardial infarction (MI), nonfatal stroke, cardiovascular death, and major bleeding (odds ratio [OR], 0.34, 95 percent confidence interval [CI], 0.20–0.59).

The same was true for recurrent MI (OR, 0.35, 95 percent CI, 0.17–0.70) and cardiovascular death (OR, 0.24, 95 percent CI, 0.10–0.58).

“Although the study included 104 patients with the loss-of-function mutation, only 31 patients had a change in drug therapy from clopidogrel to ticagrelor due to the unforeseen unavailability of ticagrelor in one of the hospitals due to economic reasons,” the researchers said.

“Despite the low rate of ticagrelor use in the genotype-guided group, CYP2C19 genotype-guided therapy significantly improved both the primary and other secondary outcomes,” they added.